Diabetes mellitus and medicationin pharmacy .pdf

By: Manar Abu Kharma (150591)
Supervised By: Dr- Raneem Al Shawabkeh
PRESENTATION FOR
HOSPITAL PHARMACY
ROTATION (PHAR641)
Diabetes Mellitus

Outline:
■ Disease definition
■ Risk factors
■ Diagnosis and screening
■ Complications
■ Non-pharmacological and pharmacological Treatment and trade
names.
■ Pregnancy category, monitoring and renal adjustment.
■ Counseling
■ References

Definition
■ Diabetes mellitus (DM): a group of chronic metabolic disorders
characterized by hyperglycemia.

Types of DM:
Type 1 DM: absolute insulin deficiency resulting from pancreatic b-cell
destruction, most commonly the result of an autoimmune process, or idiopathic.
Type 2 DM: slow, gradual onset of hyperglycemia that often is asymptomatic.
Genetic and environmental. It results from increasing insulin resistance and
impaired insulin secretion.
Gestational DM: occurs when pregnant without history of DM develops a high
blood sugar near third trimester.
Secondary DM: Disease or Drug related DM.

Screening:
■ Screening of T2DM:
■ ADA recommends screening for type 2 diabetes every 3 years in all adults
beginning at 45 years of age.
■ Testing should be considered for patients at any age who are overweight (BMI
>=25 kg/m2) and have at least one other risk factor for the development of
T2DM.
■ Gestational Diabetes screening:
■ Risk assessment performed at first prenatal visit with random glucose screen.
■ All women should be screened with an oral glucose tolerance test between weeks
24 and 28 of gestation unless they are in the low-risk category.

Diagnosis:
Prediabetes Diabetes Goal
A1C (%) 5.7% - 6.4% ≥ 6.5% <7%
Fasting (mg/dL) 100 – 125 ≥126 80-130
2-hour
postprandial/
random (mg/dL)
140 - 199 ≥ 200 <180

■ Diabetic ketoacidosis
■ Hyperosmolar hyperglycemic state
■ Hypoglycemia
Metabolic complications:

■ Diet:
Healthy diet moderate in carbohydrates and low in saturated fat and a balanced meal
delivering all of the essential vitamins and minerals is recommended in DM.
■ Physical Activity:
Aerobic exercise promotes weight reduction and improves insulin sensitivity thus
lowering blood glucose levels. Goal: at least 150 min/week of moderate intensity
exercise spread over at least 3 days a week.
■ Weight Management: weight loss or weight maintenance.
Non-pharmacological Therapy:

■ Oral medications:
■ Biguanides (metformin)
■ Sulfonylurea's (1st: acetohexamide, chlorpropamide, tolazamide and tolbutamide)
(2nd:glimepiride,glipizide,gliclazide,glyburide)
■ Meglitinides (Rapaglinide, Nataglinide)
■ Thiazolidinediones (Rosiglitazone, pioglitazone)
■ DPP-4 inhibitors (Sitagliptins, Saxagliptins, linagliptins, Alogliptins)
■ A-Glucosidase Inhibitors (Acarbose, Miglitol)
■ Sodium glucose cotransporter2 SGLT2 inhibitors (Canagliflozin, Dapagliflozin,
Empagliflozin)
■ Injectable medications:
■ Insulin.
■ Glucagon-like peptide 1 (GLP-1) Agonists (Exenatide and Liraglutide)
Pharmacological Therapy:

Considerations when selecting pharmacotherapy for type
2 diabetes:

■ MOA: Inhibits the release of glucose from the liver enhances insulin sensitivity in
liver.
■ It reduces A1C by 1.5% to 2%.
■ Strength: 500,750, 850,1000 mg.
■ Other indications: Polycystic ovary syndrome (PCOS).
■ Dose: start with 500mg twice daily and titrate the dose weekly. Maximum daily dose
2550 mg/day.
■ Side effects:
o Nausea : take with meals, and slowly titrate the dose and Use ER formula.
o Diarrhea usually subside within 7-10 days.
o Metallic taste, Interfere with vitamin B12 absorption (with long term use).
o Very rarely, lactic acidosis (drug must be D/C ) (US Boxed Warning ).
o The least one to cause hypoglycemia.
BIGUANIDES (metformin):

■ Reduces weight 2-3 kg/month and may decrease the TG, LDL by ~8-15% and modestly
increase HDL by 2%.
■ Monitor: FBS.PBG, A1C, monitor renal function (eGFR) prior to therapy initiation and
at least annually or at least every 3 to 6 months if eGFR is <60 mL/min, vitamin B12
levels every 1-2years after ≥ 4yrs on metformin.
■ Contraindicated:
o If the patient was naïve to metformin and CrCl < 45  don't initiate therapy
o If the patient was on metformin and CrCl was 30-45  decrease the dose to the half.
o If the patient was on metformin and CrCl was <30  D/C metformin (CI).
o Discontinue temporarily in patients in which intravascular iodinated contrast media are
utilized or major surgery. Hold metformin in AKI.
o SCr ≥1.4 in males and 1.5 in females mg/dl.
o Avoid metformin in liver disease is considered as its a risk factor for the development of
lactic acidosis

■ Pregnancy considerations: B, cross the placenta, but can be used in pregnancy as no adverse fetal
effects has been observed.
■ Metformin is present in breast milk but breastfeeding is considered acceptable while on it.
■ Counseling:
•Take with meals.
•Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel
well.
• HbA1c: monitor at least every 6 months in patients who have stable glycemic control; monitor every
3months if treatment goals aren’t met.
■ Extended-release tablets:
•Take with the evening meal if taking once daily.
•Swallow whole. Do not chew, break, or crush.
•If you have trouble swallowing, talk with your doctor.
■ What do I do if I miss a dose? Skip the missed dose and go back to your normal time unless your
doctor tells you to do something else. Do not take 2 doses at the same time or extra doses.

Drug strength Maximum dose
Biguanides
Metformin 500 , 850,
1000mg
There is a manufacturer
maximum dose according to the
strength:
500 mg  2 g/day
850 mg  2550 mg/day
1g  2.5 g/day
Sulfonylureas
Glyburide or
Glibenclamide 5 mg 20 mg / day
Glimepiride
1, 2, 3, 4 mg 8 mg/day
Gliclazide 60 mg
80 mg
Modified release  120mg/day
Immediate release 320 mg/day
Glipizide 5 mg 40 mg/day
Thiazolidinedione pioglitazone 15, 30, 45 mg 45 mg/day
Rosiglitazone 4mg 8 mg/day
Tables:

Drug Strength Max dose
Meglitinides
Repaglinide 0.5,1,2mg 16 mg
Nateglinide 60,120mg 360 mg
DPP-4 inhibitors
Sitagliptin 25,50,100 mg 100 mg
Saxagliptin 2.5,5 mg 5 mg
Vildagliptin - -
Linagliptin 5mg 5 mg
GLP-1 agonist
Exenatide 5, 10 mcg 20 mcg/day
Liraglutide 18mg/3mL -
a-glucosidase
inhibitors
Acarbose 25,50,100mg 100 mg tid
Miglitol 25,50,100mg 100 mg tid
Tables:

Sulfonylureas
• MOA: Increase the insulin secretion from pancreatic B cells
• A1C reduction by 1.5 to 2%
• A majority of patients will not reach glycemic goals with sulfonylurea monotherapy.
• Dose: table.
• Drug should be taken 30 min before meals and must eat after it.
• Monitor: FBG, A1c, hypoglycemia.
• Side effects: Hypoglycemia, Weight gain, increase in liver enzymes, Skin rash, GI upset (Nausea,
vomiting, constipation, gastric discomfort).Headache & flu like symptoms.
• When given in equipotent doses, all SU are equally effective at lowering BG.
• Most hypoglycemic agent is Glyburide. So, avoid in geriatric.
• Least Hypoglycemic agent: Gliclazide (prefer in geriatric)
• Glipizide is a preferred sulfonylurea in patients with chronic kidney disease (it has inactive metabolites)
• Contraindicated: in case of sulfa allergy,G6PD.CrCl<15.
• Not given in pregnancy or in lactating women, children or sever Renal or Hepatic impairment.

1) Glimepiride :
o Dose Initially, 1 mg once daily, adjusted according to response in 1 mg steps at 1–2
week intervals up to 4 mg once daily.
o In CrCl 15-60ml/min: initiate a lower dose (1mg daily) and titrate cautiously. Crcl <
15ml/min: Avoid use.
o Available in market:
“Amaryl (1.2.3.4) , glemax (2.3.4.6), glimeryl(1.2.3.4 ). Dipride (1.2.3.4) “

2) Gliclazide:
 Dose: 40–320 mg daily in 1–2 doses; up to 160 mg as single dose.
Controlled release formulation, initially 30 mg once daily; increase dose, according to response,
by 30 mg once daily at not less than 2-week intervals; maximum daily dose 120 mg.
-CI in pregnancy and breastfeeding.
-CrCl=15 to 60 mL/min: Use with caution. IR tablet: Initial: 40 once daily; may gradually
increase dose in 40 mg increments every 2 to 4 weeks if needed .
MR tablet: Initial: 30 once daily; may increase dose in 30 mg increments every 2 to 4 weeks.
Available in market :
 GLICLAZIDE TABS 30 MG (DEBADAY MR®, DIAMICRON MR®)
 GLICLAZIDE TABS 80 MG (DEBADAY®, DIAMICRON®, DIAMID®, MICROZIDE®)

3) Glipizide:
 Dose: initially 2.5–5 mg daily, adjusted according to response;
max. 20 mg daily; up to 15 mg may be given as a single dose;
higher doses divided.
 Products:
Glipizide TABS 5 MG (Glipizide®, Minodiab®).
-CrCl 10 to <50 mL/minute/1.73 m2: Initial: 2.5 mg once daily.
May cautiously titrate based on glycemic control up to a maximum
20 mg/day.
-Crcl <10 mL/minute/1.73 m2: Avoid use if possible
-Not used in pregnancy but breastfeeding is encouraged.
4) Tolbutamide:
- Dose: 0.5–1.5 g (max. 2 g) daily in divided doses or as a
single dose with or immediately after breakfast.
- Products: Tolbutamide 500 mg tablets.

5) Glibenclamide “glyburide”
 Dose  2.5–20 mg daily in 1–2 doses; up to 10 mg as single dose.
 Products:
GLIBENCLAMIDE TABS 5 MG (DAONIL®, EUGLUCON®, GLIBEMIDE®, GLIBESYN®,
GLIBIL®, GLUCANA®,GLUCOMID®, GLUNIL®, MELIX®, RIVECLAMIDE®).

Counseling:
•Take with the first meal of the day, if taking once a day.
•Take this drug at the same time of day.
•Keep taking this drug as you have been told by your doctor or other health care
provider, even if you feel well.
-Low blood sugar may happen with this drug. Do not drive if your blood sugar has been
low.
• For regular release:
•Take a missed dose as soon as you think about it, with a meal.
•If it is close to the time for your next dose, skip the missed dose and go back to your
normal time.
•Do not take 2 doses at the same time or extra doses.
• Modified-release tablets:
•Skip the missed dose and go back to your normal time.
•Do not take 2 doses at the same time or extra doses.
Sulfonylureas

MEGLITINIDES
■ MOA: increase insulin secretion from the B cells of the pancreas.
■ Example : 1)Repaglinide 2) Nateglinide
■ NA in Jordan
■ A1C reduction by (0.6%-1%)
■ Rapid acting and Short acting.
■ Indications Type 2 diabetes, as monotherapy or combined with metformin or
insulin.
■ If the meal is skipped, the medication can be skipped. Taken 15-30 minutes
before eating.
■ Side effects: hypoglycemia, weight gain, nausea or vomiting, Headache.
■ CrCl <20: may be used in patients with renal or hepatic insufficiency (no
adjustment).
■ Not to be used in pregnancy or breastfeeding (present in breast milk).

THIAZOLIDINEDIONES(glitazones)
o MOA: they activate the PPAR-γ which are primarily located on fat cells and
vesicular cells. Increases the sensitivity of peripheral tissues to insulin; decrease
hepatic glucose output.
o Reduce HbA1C values ~1% to 1.5% and reduce FPG levels by ~60 to 70 mg/dl.
o Maximal glycemic-lowering effects may not be seen until 3 to 4 months of
therapy .
 Dosage:
1. Pioglitazone : 15–30 mg once daily; may be increased to a maximum dose of 45 mg
once daily after 6–8 weeks of treatment if effect is inadequate.
2. Rosiglitazone :4 mg/day increase after 8–12 weeks to maximum of 8 mg/day .
o Taken with or without regard to meal.
o Maximum glycemic-lowering effect may not be seen until 3 to 4 months of therapy.
o Monitor: FBG, A1C%, signs of fluid retention or HF, liver enzymes.

o Pioglitazone : TG HDL
o Rosiglitazone : LDL HDL
o Side effects: fluid retention, dilutional anemia, weight gain, increased
fracture, bladder cancer .
o CI: Acute HF (decompensated HF) , Advanced HF (stage 3 or 4)
o NOTE: If ALT 3 times higher from upper limit ……. D/C.
If give drug with gemfibrozil …… decrease dose .
o Altered kidney function: Mild to severe impairment: No dosage
adjustment
o Not recommended in pregnancy. Not known if present in breast milk.
THIAZOLIDINEDIONES (glitazones)

1. Saxagliptin (Onglyza) 2.5-5 mg once daily
2. Sitagliptin (Januvia)
3. Linagliptin (trajenta)
4. Vildagliptin (Galvus)
5. Alogliptin (vipidia )
• MOA: they prolong the half life of endogenously produce GLP-1 and GIP.
• A1C reduction by 0.7 to 1%
• Indications: Type 2 diabetes mellitus as monotherapy, dual therapy in combination with either
metformin, pioglitazone, a sulfonylurea, or insulin (when treatment with these drugs alone fails to
achieve adequate glycemic control), or as triple therapy in combination with metformin and
either pioglitazone or insulin.
• Taken without regard to meal.
• Linagliptin has no renal dose adjustment.
• Saxagliptin if Crcl <45 mL/minute/1.73 m2: 2.5 mg once daily.
• Sitagliptin if Crcl ≥30 to <45 mL/minute/1.73 m2: 50 mg once daily.
DIPEPTIDYL-PEPTIDASE 4 (DPP-4) INHIBITORS (gliptins)

• Possible side effects: upper respiratory tract infection, sore throat ,headache
nasopharyngitis, urtecria, no significant GI effects.
• Monitor: A1C, renal function and signs & symptoms of pancreatitis ( Abdominal
discomfort, pain, shock and respiratory distress ).
• DPP-4 inhibitors not used in pregnancy and not known present in breast milk.
DIPEPTIDYL-PEPTIDASE 4 (DPP-4) INHIBITORS (gliptins)
Sitagliptin
Vildagliptin
Saxagliptin
Linagliptin

Sodium Glucose cotransporter 2 (SGLT2) inhibitors
■ MOA: They help in eliminating glucose in the urine by blocking SGLT protein. Also, they increase
insulin sensitivity.
 Canagliflozin“ Invokana “
 Dapagliflozin “ferxiga”
 Empagliflozin. “Jardiance “
■ May promote weight loss and lower the blood pressure.
■ Administration before the first meal.
■ Monitor: K, SCr, urine analysis,BP, blood glucose.
■ Side effects: hyperkalemia, ketoacidosis, increase urination, genital and UT infections, AKI, CKD.
lower limb amputation (canagliflozin), bone fracture, hypotension and hypovolemia.
■ Contraindication: chronic kidney disease, end stage renal disease(dialysis). CrCl<30 ml/min
■ SGLT2 inhibitors not recommended in pregnancy. Not known if SGLT2i present in breast milk.

Empagliflozin:
Dapagliflozin:
Sodium Glucose cotransporter 2 (SGLT2) inhibitors
Canagliflozin:

 Acarbose and miglitol.
 MOA: inhibit the enzymes (maltase, isomaltase, sucrose, and glucoamylase) in the small
intestine, delaying the breakdown of sucrose and complex carbohydrates.
 It affects more postprandial sugar that is why they should be administered with the first bite
of meal.
 HbA1C reduction of 0.3% to 1%.
 Both α-glucosidase inhibitors should be taken with the first bite of the meal so that drug may
be present to inhibit enzyme activity.
 CrCl < 25ml/min use is not recommended for both agents.
 Limited information about use in pregnancy so its not used. It is not known if acarbose is
present in breast milk but meglitol is present but not recommended.
ALPHA-GLUCOSIDASE INHIBITORS:

Side effects (self-limited within weeks): GI such as flatulence, bloating, abdominal
discomfort, and diarrhea.
Monitor: HbA1C, SCr, periodic blood glucose and serum transaminase (only with Acarbose)
every 3 months during the first year then periodically thereafter.
CI in IBD or if SCr >2mg/dl , intestinal obstruction, cirrhosis, DKA.
ALPHA-GLUCOSIDASE INHIBITORS:

Injectables: GLUCAGON-LIKE PEPTIDE -1
■ Exenatide (Byetta): “Injected 60 min before meal twice daily”
 Exenatide extended release (Bydureon) “2 mg SQ once every 7 days “
 Liraglutide (Victoza): once daily
 Stimulate the release of insulin and Used with metformin and sulfonylurea and suppress
elevated glucagon.
 They increase satiety, slows gastric emptying, and promotes weight loss.
 It decreases postprandial glucose more than the fasting.
■ Exenatide is detectable in plasma within 10 to 15 minutes after SQ injection, it has tmax of 2
hours and a duration of 6 hours, and can be given once weekly.
■ Eventide can delay the absorption of other drugs. Not recommended if CrCl<30.
■ Liraglutide is dosed once daily and may be given regardless of meals. Its used for obesity
because it decrease weight. No renal dose adjustment.
■ Both drugs have Black box warning about thyroid C cells tumors.

Liraglutide
GLUCAGON-LIKE PEPTIDE -1
• S/E : Nausea or vomiting , Headache ,Dizziness , Increased risk of inflamed
pancreas (pancreatitis) and some thyroid tumors.
• Monitor: A1C, renal function, weight, TG and signs & symptoms of pancreatitis
• GLP-1 agonist not recommended in pregnancy and not known present in breast
milk.
Exenatide

■ It is a polypeptide hormone secreted by pancreatic beta-cells. Insulin increases
glucose uptake by adipose tissue and muscles and suppresses hepatic glucose
release. The role of insulin is to lower blood-glucose concentrations in order to
prevent hyperglycemia and its associated microvascular, macrovascular and metabolic
complications.
■ Insulin therapy decreases the micro and macro-vascular complications.
■ Mainly used for Type 1 DM and for uncontrolled type 2 DM.
■ SE: hypoglycemia and weight gain.
■ Dosing (individualized): T1DM, the average daily requirement for insulin is 0.5 to
0.6 unit/kg, 50% : basal and 50% dedicated to meal coverage “bolus”
■ The bolus or prandial insulin component can be regular insulin, lispro, aspart, or
glulisine injected before meals.
■ Basal insulin component: including once- or twice-daily NPH, detemir, or glargine.
■ NPH, Detemir, lispro and aspart are commonly used safely for GDM based on trials.
Insulin:

Insulin:
Insulin
Rapid
acting
Lispro
(Humolog)
Aspart
(Novorapid,
Novolog)
Glulisine
(Apidra)
Regular
insulin (Short)
HumolinR,
Novolin R.
Actrarapid
Intermediate
acting insulin
(NPH)
Long acting
insulin
Glargine
(lantus)
Detemir
(levemir)
Degludec
(Tersiba)

Insulin:
 No renal dose adjustment for insulin just monitor for BG.
 Counseling points:
 Its clear solution that given SC .
 short onset of action allows them to be given immediately before meals” take it (5-15)
min before meal
 If patient skip meal skip dose

 Short acting insulin (Regular):
1. actrapid 100 IU/ml solution .
2. actrapid HM Penfills100 IU/ml solution
3. Humulin R 100 IU/ml
4. Novolin R.
Give 30 minute before meal

 Intermediate-Acting Insulins products:
- INSULIN, HUMAN, BIPHASIC ASPART, RECOMBINANT HUMAN INSULIN ANALOGUE 100 IU/ML
(30% INSULIN ASPART+70% INSULIN ASPART PROTAMINE) (NOVOMIX®)
-INSULIN Regular, NPH insulin[100 IU/ML (30+70)] 3 ML (GENSULIN M 30®, MIXTARD 30®)
- INSULIN, HUMAN, ISOPHANE VIAL 100 IU/ML 10 ML VIAL (HUMULIN NPH®, GENSULIN N®,
INSULATARD®)
-INSULIN, HUMAN, ISOPHANE VIAL 100 IU/ML 10 ML VIAL (GENSULIN M 30®, HUMILIN
70/30®, MIXTARD 30®).

Insulin Glulisine
Aspart
Insulin human
Novomix:
1 ml of the suspension contains 100 units
soluble insulin aspart*/protamine-
crystallised insulin aspart* in the ratio
30/70

Counselling points for intermediate :
 (cloudy solution) have a prolonged duration of action .
 Given (30-45) min before meals .
 Shake it gently before use

Long-acting insulin products:
-INSULIN, HUMAN, DETEMIR, RECOMBINANT HUMAN INSULIN ANALOGUE 100
IU/ML (LEVEMIR®).
-INSULIN, HUMAN, GLARGINE, RECOMBINANT HUMAN INSULIN ANALOGUE 100
IU/ML (LANTUS®).
 Can be taken any time of the day, preferred to be before bed time.

■ Don’t freeze
■ Don’t use after expiration date on the vial or pen supplied from the manufacturer.
■ Don’t expose insulin to direct heat or light.
■ Unopened insulin should be stored in the door of the fridge (8-25%).
■ Open insulin can be stored at room temperature.
■ Opened insulin should be used within 28 days.
■ Don’t use insulin if changed in color.
Insulin storage:

Instruction to inject insulin:

■ The insulin needs to go into the fat layer under the skin
■ Pinch the skin and put the needle in at a 90º angle.
■ Use clean site. don’t put alcohol on the site
■ Push the needle all the way into the skin.
■ Leave the syringe in place for 5 seconds after injecting.
■ Change the site of injection to prevent your skin may start to become stiffer, often described
as being ‘lumpy’ lipohypertrophy.
Counseling points about insulin:

• Sign and symptoms: sweating, nausea and vomiting, dizziness, fatigue,
sweating, double vision, palpitations, increase hunger or thirst, tremors, cold
extremities ,and finally loss of consciousness.
Taking of any sugared drink, or one spoonful (15g) sugar dissolved in a cup
of water. Wait for 15min measure the BG levels, if no response retry by
sweetened beverages for up to three trials. If no response go to the
emergency department to receive 1mg of IM or SC glucagon. If there is
established IV access give IV glucose.
Hypoglycemia:

References:
■ Lexicomp
■ Dipiro 11
■ Uptodate

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